AML-VAC-XS15-01: Multi-peptide vaccination adjuvanted with the TLR1/2 ligand XS15 in acute myeloid leukemia (AML) patients who have achieved complete remission with first line therapy

Start Date14 Aug 2024

Sponsor / Collaborator-

NCT04842513 / RecruitingPhase 1IIT

Multi Peptide Vaccination With Pam3Cys-GDPKHPKSF (XS15) as an Immunomodulator in Addition to Standard Postoperative Radiation Therapy and Temozolomide Chemotherapy in Newly Diagnosed HLA-A2-positive MGMT-methylated Glioblastoma

Newly diagnosed HLA-A2-positive MGMT-methylated glioblastoma patients will be vaccinated with a Multi peptide vaccination with Pam3Cys-GDPKHPKSF (XS15) as an immunomodulator in addition to standard postoperative radiation therapy and temozolomide chemotherapy to assess immunogenicity, efficacy, safety of the combination of multipeptide vaccination and the immune modulator XS15 emulsified in Montanide ISA 51 VG

Start Date03 May 2021

Sponsor / Collaborator

University Hospital Tübingen

NCT04688385 / Active, not recruitingPhase 1IIT

iVAC-XS15-CLL01: Personalized Multi-peptide Vaccination in Combination With the TLR1/2 Ligand XS15 in CLL Patients Undergoing Ibrutinib-based Regimes

The aim of this study is to evaluate the efficiency along with safety and toxicity of a personalizied multi-peptide vaccine in combination with the TLR1/2 ligand XS15 in CLL patients undergoing ibrutinib-based regimes.

Start Date23 Dec 2020

Sponsor / Collaborator

University Hospital Tübingen

100 Clinical Results associated with XS-15

100 Translational Medicine associated with XS-15

100 Patents (Medical) associated with XS-15

Literatures (Medical) associated with XS-15

27 Jan 2022·NatureQ1 · CROSS-FIELD

A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity

Q1 · CROSS-FIELD

Article

Author: Rammensee, Hans-Georg ; Marconato, Maddalena ; Richter, Marion ; Anton, Leonard ; Wacker, Marcel ; Peter, Andreas ; Bilich, Tatjana ; Meisner, Christoph ; Salih, Helmut R ; Karbach, Julia ; Rieth, Jonas ; Klein, Reinhild ; Jäger, Elke ; Walz, Juliane S ; Heitmann, Jonas S ; Bauer, Jens ; Roerden, Malte ; Fischer, Imma ; Maringer, Yacine ; Tandler, Claudia ; Hörber, Sebastian ; Nelde, Annika ; Jäger, Simon ; Reusch, Julia ; Löffler, Markus W ; Denk, Monika ; Weber, Lisa Marie

AbstractT cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18–80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4+ and CD8+ T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.

01 Dec 2019·Cancer Immunology, Immunotherapy

Combining alpha radiation-based brachytherapy with immunomodulators promotes complete tumor regression in mice via tumor-specific long-term immune response

Article

Author: Nair, Sujit S ; Kelson, Itzhak ; Efrati, Margalit ; Rammensee, Hans-Georg ; Tewari, Ashutosh ; Domankevich, Vered ; Schmidt, Michael ; Keisari, Yona ; Cohen, Adi

AbstractDiffusing alpha-emitters radiation therapy (DaRT) is the only known method for treating solid tumors with highly destructive alpha radiation. More importantly, as a monotherapy, DaRT has been shown to induce a systemic antitumor immune response following tumor ablation. Here, immunomodulatory strategies to boost the antitumor immune response induced by DaRT, and the response specificity, were investigated in the colon cancer CT26 mouse model. Local treatment prior to DaRT, with the TLR3 agonist poly I:C, was sufficient to inhibit tumor growth relative to poly I:C or DaRT alone. DaRT used in combination with the TLR9 agonist CpG, or with the TLR1/2 agonist XS15 retarded tumor growth and increased tumor-rejection rates, compared to DaRT alone, curing 41% and 20% of the mice, respectively. DaRT in combination with CpG, the Treg inhibitor cyclophosphamide, and the MDSC inhibitor sildenafil, cured 51% of the animals, compared to only 6% and 0% cure when immunomodulation or DaRT was used alone, respectively. Challenge and Winn assays revealed that these high cure rates involved a specific immunological memory against CT26 antigens. We suggest that DaRT acts in synergy with immunomodulation to induce a specific and systemic antitumor immune response. This strategy may serve as a safe and efficient method not only for tumor ablation, but also for in situ vaccination of cancer patients.

01 Dec 2019·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer

Q2 · MEDICINE

ArticleOA

Author: Rusch, Elisa ; Di Marco, Moreno ; Chandran, P Anoop ; Haen, Sebastian P ; Walz, Juliane S ; Klein, Reinhild ; Wiesmüller, Karl-Heinz ; Metzler, Gisela ; la Fougère, Christian ; Tunger, Antje ; Artzner, Kerstin ; Laske, Karoline ; Müller, Luise ; Pichler, Bernd J ; Jakobi, Meike ; Bödder, Johanna ; Zelba, Henning ; Weber, Alexander N R ; Schmitz, Marc ; Gouttefangeas, Cécile ; Schwenck, Johannes ; Gloria, Yamel Cardona ; Forchhammer, Stephan ; Schertel, Jill-Marie ; Weide, Benjamin ; Stevanović, Stefan ; Kießler, Maximilian ; Schneiderhan-Marra, Nicole ; Bauer, Jürgen ; Rammensee, Hans-Georg ; Schuster, Heiko ; Wehner, Rebekka ; Schippert, Wilfried ; Kneilling, Manfred ; Löffler, Markus W ; Backert, Linus ; Kowalewski, Daniel J

BACKGROUNDWe previously showed that the bacterial lipopeptide Pam₃Cys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8⁺ T cells in mice, when covalently coupled to a synthetic peptide.CASE PRESENTATIONWe now designed a new water-soluble synthetic Pam₃Cys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8⁺ T and NK cells by 6-sulfo LacNAc⁺ monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging. XS15 induced strong ex vivo CD8⁺ and T_H1 CD4⁺ responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide™ ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4⁺ and CD8⁺ effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 10⁵ in the granuloma and 20.5 × 10⁶ in peripheral blood.CONCLUSIONThus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.

100 Deals associated with XS-15

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma Multiforme	Phase 1	DE	University Hospital Tübingen	03 May 2021
Chronic Lymphocytic Leukemia	Phase 1	DE	University Hospital Tübingen	23 Dec 2020
Neoplasms	Preclinical	-	Emc Microcollections GmbH	-
Neoplasms	Preclinical	-	Universitaetsklinikum Tuebingen	-

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